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Journal of Clinical Microbiology, August 2004, p. 3475-3482, Vol. 42, No. 8
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.8.3475-3482.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Interlaboratory Comparison of Results of Susceptibility Testing with Caspofungin against Candida and Aspergillus Species

Frank C. Odds,1* Mary Motyl,2 Roberto Andrade,3 Jacques Bille,4 Emilia Cantón,5 Manuel Cuenca-Estrella,6 Amanda Davidson,1 Christian Durussel,4 David Ellis,7 Elyse Foraker,8 Annette W. Fothergill,9 Mahmoud A. Ghannoum,10 Robert A. Giacobbe,2 Miguel Gobernado,5 Rosemary Handke,7 Michel Laverdière,11 Wendy Lee-Yang,12 William G. Merz,13 Luis Ostrosky-Zeichner,3 Javier Pemán,5 Sophia Perea,13 John R. Perfect,14 Michael A. Pfaller,15 Laurie Proia,16 John H. Rex,3,{dagger} Michael G. Rinaldi,9 Juan-Luis Rodriguez-Tudela,6 Wiley A. Schell,14 Christine Shields,13 Deanna A. Sutton,9 Paul E. Verweij,17 and David W. Warnock12

Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Aberdeen AB25 2ZD, United Kingdom,1 Merck Research Laboratories, Whitehouse Station, New Jersey,2 University of Texas-Houston Medical School, Houston, Texas 77030,3 Clinical Microbiology Laboratory, University Hospital, 1011 Lausanne, Switzerland,4 Service of Microbiology, University Hospital La Fe, 46009 Valencia,5 National Centre for Microbiology, Instituto de Salud Carlos III, 28220 Majadahonda, Spain,6 Mycology Unit, Women's and Children's Hospital, Adelaide, Australia,7 Infectious Disease Laboratory, Christiana Care Health Services, Wilmington, Delaware 19801,8 Fungus Testing Laboratory, Department of Pathology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900,9 Center for Medical Mycology, Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106-5028,10 Department of Microbiology-Infectious Diseases, Hopital Maisonneuve- Rosemont, Montréal, Quebec H1T 2M4, Canada,11 Mycotic Diseases Branch, Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333,12 The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-7093,13 Duke University Medical Center, Durham, North Carolina 27710,14 Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242,15 Section of Infectious Diseases, Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612,16 Medical Microbiology, UMC St. Radboud, 6500 HB Nijmegen, The Netherlands,17

Received 5 November 2003/ Returned for modification 12 January 2004/ Accepted 7 May 2004

Seventeen laboratories participated in a study of interlaboratory reproducibility with caspofungin microdilution susceptibility testing against panels comprising 30 isolates of Candida spp. and 20 isolates of Aspergillus spp. The laboratories used materials supplied from a single source to determine the influence of growth medium (RPMI 1640 with or without glucose additions and antibiotic medium 3 [AM3]), the same incubation times (24 h and 48 h), and the same end point definition (partial or complete inhibition of growth) for the MIC of caspofungin. All tests were run in duplicate, and end points were determined both spectrophotometrically and visually. The results from almost all of the laboratories for quality control and reference Candida and Aspergillus isolates tested with fluconazole and itraconazole matched the NCCLS published values. However, considerable interlaboratory variability was seen in the results of the caspofungin tests. For Candida spp. the most consistent MIC data were generated with visual "prominent growth reduction" (MIC2) end points measured at 24 h in RPMI 1640, where 73.3% of results for the 30 isolates tested fell within a mode ± one dilution range across all 17 laboratories. MIC2 at 24 h in RPMI 1640 or AM3 also gave the best interlaboratory separation of Candida isolates of known high and low susceptibility to caspofungin. Reproducibility of MIC data was problematic for caspofungin tests with Aspergillus spp. under all conditions, but the minimal effective concentration end point, defined as the lowest caspofungin concentration yielding conspicuously aberrant hyphal growth, gave excellent reproducibility for data from 14 of the 17 participating laboratories.

* Corresponding author. Mailing address: Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Aberdeen AB25 2ZD, United Kingdom. Phone: (44) 1224-273128. Fax: (44) 1224-273144. E-mail: f.odds{at}abdn.ac.uk.

{dagger} Present address: AstraZeneca, Alderley Park, Manchester, United Kingdom.

Journal of Clinical Microbiology, August 2004, p. 3475-3482, Vol. 42, No. 8
0095-1137/04/$08.00+0     DOI: 10.1128/JCM.42.8.3475-3482.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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